11-66624440-G-T

Position:

• chr11-66624440-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006328.4(RBM14):​c.564G>T​(p.Gln188His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RBM14 NM_006328.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.51

Genes affected

RBM14 (HGNC:14219): (RNA binding motif protein 14) This gene encodes a ribonucleoprotein that functions as a general nuclear coactivator, and an RNA splicing modulator. This protein contains two RNA recognition motifs (RRM) at the N-terminus, and multiple hexapeptide repeat domain at the C-terminus that interacts with thyroid hormone receptor-binding protein (TRBP), and is required for transcription activation. Alternatively spliced transcript variants encoding different isoforms (with opposing effects on transcription) have been described for this gene. [provided by RefSeq, Oct 2011]

RBM14-RBM4 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26110038).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBM14	NM_006328.4	c.564G>T	p.Gln188His	missense_variant	2/3	ENST00000310137.5
RBM14-RBM4	NM_001198845.2	c.337+7383G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBM14	ENST00000310137.5	c.564G>T	p.Gln188His	missense_variant	2/3	1	NM_006328.4	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 25, 2024

The c.564G>T (p.Q188H) alteration is located in exon 2 (coding exon 2) of the RBM14 gene. This alteration results from a G to T substitution at nucleotide position 564, causing the glutamine (Q) at amino acid position 188 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.26	T
MetaSVM	Uncertain	0.033	D
MutationAssessor	Benign	0.81	L
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.24	N
REVEL	Uncertain	0.38
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.26	T
Polyphen		0.99	D
Vest4		0.44
MutPred		0.23		Gain of glycosylation at T184 (P = 0.1876);
MVP		0.21
MPC		0.12
ClinPred		0.53	D
GERP RS		4.9
Varity_R		0.13
gMVP		0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-66391911;